The complement receptor of B lymphocytes is expressed evidently late during development of the B cell lineage. Functional studies in vivo and in vitro have shown that both CR plus ("late") and CR minus ("early") B lymphocytes are capable of producing antibody. The central question of this proposal is whether CR minus populations can differentiate to plaque forming cells (PFC) without passing through a CR plus differentiative state, or whether the CR plus state is an obligatory intermediary. Since the in vitro immune response requires the complex interaction of several cell types (which may obscure the issue of B cell differentiation), we propose to use LPS for polyclonal activation of B cells in the absence of accessory cells. We will determine the kinetics of initiation of Ig synthesis in isolated Cr minus and CR plus B cell populations. Starting with CR minus B cells, we will induce CR by culturing with LPS, and test whether after removal of CR plus cells Ig synthesis is delayed. Based on our observation that factors derived from helper T cells induce differentiation in early B cells, we will investigate the significance of an intact T cell compartment for the maturation of B cells. We will analyze the state of B cell maturity in T cell deficient mice and attempt to reconstitute the T cell compartment if defects in the B cell lineage become apparent.